Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma.

Cancer Genome Atlas Research Network. Electronic address: andrew_aguirre@dfci.harvard.edu; Cancer Genome Atlas Research Network; Raphael, Benjamin J; Hruban, Ralph H; Aguirre, Andrew J; Moffitt, Richard A; Yeh, Jen Jen; Stewart, Chip; Robertson, A Gordon; Cherniack, Andrew D; Gupta, Manaswi; Getz, Gad; Gabriel, Stacey B; Meyerson, Matthew; Cibulskis, Carrie; Fei, Suzanne S; Hinoue, Toshinori; Shen, Hui; Laird, Peter W; Ling, Shiyun; Lu, Yiling; Mills, Gordon B; Akbani, Rehan; Loher, Phillipe; Londin, Eric R; Rigoutsos, Isidore; Telonis, Aristeidis G; Gibb, Ewan A; Goldenberg, Anna; Mezlini, Aziz M; Hoadley, Katherine A; Collisson, Eric; Lander, Eric; Murray, Bradley A; Hess, Julian; Rosenberg, Mara; Bergelson, Louis; Zhang, Hailei; Cho, Juok; Tiao, Grace; Kim, Jaegil; Livitz, Dimitri; Leshchiner, Ignaty; Reardon, Brendan; Van Allen, Eliezer; Kamburov, Atanas; Beroukhim, Rameen; Saksena, Gordon; Schumacher, Steven E; Noble, Michael S; Heiman, David I; Gehlenborg, Nils; Kim, Jaegil; Lawrence, Michael S; Adsay, Volkan; Petersen, Gloria; Klimstra, David; Bardeesy, Nabeel; Leiserson, Mark D M; Bowlby, Reanne; Kasaian, Katayoon; Birol, Inanc; Mungall, Karen L; Sadeghi, Sara; Weinstein, John N; Spellman, Paul T; Liu, Yuexin; Amundadottir, Laufey T; Tepper, Joel; Singhi, Aatur D; Dhir, Rajiv; Paul, Drwiega; Smyrk, Thomas; Zhang, Lizhi; Kim, Paula; Bowen, Jay; Frick, Jessica; Gastier-Foster, Julie M; Gerken, Mark; Lau, Kevin; Leraas, Kristen M; Lichtenberg, Tara M; Ramirez, Nilsa C; Renkel, Jeremy; Sherman, Mark; Wise, Lisa; Yena, Peggy; Zmuda, Erik; Shih, Juliann; Ally, Adrian; Balasundaram, Miruna; Carlsen, Rebecca; Chu, Andy; Chuah, Eric; Clarke, Amanda; Dhalla, Noreen; Holt, Robert A; Jones, Steven J M; Lee, Darlene; Ma, Yussanne; Marra, Marco A; Mayo, Michael; Moore, Richard A; Mungall, Andrew J; Schein, Jacqueline E; Sipahimalani, Payal; Tam, Angela; Thiessen, Nina; Tse, Kane; Wong, Tina; Brooks, Denise; Auman, J Todd; Balu, Saianand; Bodenheimer, Tom; Hayes, D Neil; Hoyle, Alan P; Jefferys, Stuart R; Jones, Corbin D; Meng, Shaowu; Mieczkowski, Piotr A; Mose, Lisle E; Perou, Charles M; Perou, Amy H; Roach, Jeffrey; Shi, Yan; Simons, Janae V; Skelly, Tara; Soloway, Matthew G; Tan, Donghui; Veluvolu, Umadevi; Parker, Joel S; Wilkerson, Matthew D; Korkut, Anil; Senbabaoglu, Yasin; Burch, Patrick; McWilliams, Robert; Chaffee, Kari; Oberg, Ann; Zhang, Wei; Gingras, Marie-Claude; Wheeler, David A; Xi, Liu; Albert, Monique; Bartlett, John; Sekhon, Harman; Stephen, Yeager; Howard, Zaren; Judy, Miller; Breggia, Anne; Shroff, Rachna T; Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu; Wu, Ye; Jennifer, Smith; Roggin, Kevin; Becker, Karl-Friedrich; Behera, Madhusmita; Bennett, Joseph; Boice, Lori; Burks, Eric; Carlotti Junior, Carlos Gilberto; Chabot, John; Pretti da Cunha Tirapelli, Daniela; Sebastião Dos Santos, Jose; Dubina, Michael; Eschbacher, Jennifer; Huang, Mei; Huelsenbeck-Dill, Lori; Jenkins, Roger; Karpov, Alexey; Kemp, Rafael; Lyadov, Vladimir; Maithel, Shishir; Manikhas, Georgy; Montgomery, Eric; Noushmehr, Houtan; Osunkoya, Adeboye; Owonikoko, Taofeek; Paklina, Oxana; Potapova, Olga; Ramalingam, Suresh; Rathmell, W Kimryn; Rieger-Christ, Kimberly; Saller, Charles; Setdikova, Galiya; Shabunin, Alexey; Sica, Gabriel; Su, Tao; Sullivan, Travis; Swanson, Pat; Tarvin, Katherine; Tavobilov, Michael; Thorne, Leigh B; Urbanski, Stefan; Voronina, Olga; Wang, Timothy; Crain, Daniel; Curley, Erin; Gardner, Johanna; Mallery, David; Morris, Scott; Paulauskis, Joseph; Penny, Robert; Shelton, Candace; Shelton, Troy; Janssen, Klaus-Peter; Bathe, Oliver; Bahary, Nathan; Slotta-Huspenina, Julia; Johns, Amber; Hibshoosh, Hanina; Hwang, Rosa F; Sepulveda, Antonia; Radenbaugh, Amie; Baylin, Stephen B; Berrios, Mario; Bootwalla, Moiz S; Holbrook, Andrea; Lai, Phillip H; Maglinte, Dennis T; Mahurkar, Swapna; Triche, Timothy J; Van Den Berg, David J; Weisenberger, Daniel J; Chin, Lynda; Kucherlapati, Raju; Kucherlapati, Melanie; Pantazi, Angeliki; Park, Peter; Saksena, Gordon; Voet, Doug; Lin, Pei; Frazer, Scott; Defreitas, Timothy; Meier, Sam; Chin, Lynda; Kwon, Sun Young; Kim, Yong Hoon; Park, Sang-Jae; Han, Sung-Sik; Kim, Seong Hoon; Kim, Hark; Furth, Emma; Tempero, Margaret; Sander, Chris; Biankin, Andrew; Chang, David; Bailey, Peter; Gill, Anthony; Kench, James; Grimmond, Sean; Johns, Amber; Cancer Genome Initiative Apgi, Australian Pancreatic; Postier, Russell; Zuna, Rosemary; Sicotte, Hugues; Demchok, John A; Ferguson, Martin L; Hutter, Carolyn M; Mills Shaw, Kenna R; Sheth, Margi; Sofia, Heidi J; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zhang, Jiashan Julia; Felau, Ina; Zenklusen, Jean C     «

Cancer Genome Atlas Research Network. Electronic address: andrew_aguirre@dfci.harvard.edu; Cancer Genome Atlas Research Network; Raphael, Benjamin J; Hruban, Ralph H; Aguirre, Andrew J; Moffitt, Richard A; Yeh, Jen Jen; Stewart, Chip; Robertson, A Gordon; Cherniack, Andrew D; Gupta, Manaswi; Getz, Gad; Gabriel, Stacey B; Meyerson, Matthew; Cibulskis, Carrie; Fei, Suzanne S; Hinoue, Toshinori; Shen, Hui; Laird, Peter W; Ling, Shiyun; Lu, Yiling; Mills, Gordon B; Akbani, Rehan; Loher, Phillipe; Lo...     »

We performed integrated genomic, transcriptomic, and proteomic profiling of 150 pancreatic ductal adenocarcinoma (PDAC) specimens, including samples with characteristic low neoplastic cellularity. Deep whole-exome sequencing revealed recurrent somatic mutations in KRAS, TP53, CDKN2A, SMAD4, RNF43, ARID1A, TGF?R2, GNAS, RREB1, and PBRM1. KRAS wild-type tumors harbored alterations in other oncogenic drivers, including GNAS, BRAF, CTNNB1, and additional RAS pathway genes. A subset of tumors harbored multiple KRAS mutations, with some showing evidence of biallelic mutations. Protein profiling identified a favorable prognosis subset with low epithelial-mesenchymal transition and high MTOR pathway scores. Associations of non-coding RNAs with tumor-specific mRNA subtypes were also identified. Our integrated multi-platform analysis reveals a complex molecular landscape of PDAC and provides a roadmap for precision medicine.     «

We performed integrated genomic, transcriptomic, and proteomic profiling of 150 pancreatic ductal adenocarcinoma (PDAC) specimens, including samples with characteristic low neoplastic cellularity. Deep whole-exome sequencing revealed recurrent somatic mutations in KRAS, TP53, CDKN2A, SMAD4, RNF43, ARID1A, TGF?R2, GNAS, RREB1, and PBRM1. KRAS wild-type tumors harbored alterations in other oncogenic drivers, including GNAS, BRAF, CTNNB1, and additional RAS pathway genes. A subset of tumors harbore...     »